D-dopachrome tautomerase in adipose tissue inflammation and wound repair.

Abstract

D-dopachrome tautomerase (D-DT/MIF-2) is a member of the macrophage migration inhibitory factor (MIF) cytokine superfamily, and a close structural homolog of MIF. MIF and D-DT have been reported to be involved in obesity, but there is little known about the regulation of D-DT in adipose tissue inflammation and wound healing. Subcutaneous adipose tissue was collected from 54 healthy donors and 28 donors with acutely inflamed wounds undergoing wound debridement. In addition, epididymal fat pads of mice were injected with lipopolysaccharide to study receptor expression and cell migration in vivo. D-DT protein levels and mRNA expression were significantly decreased in subcutaneous adipose tissue adjacent to acutely inflamed wounds. D-DT improved fibroblast viability and increased proliferation in vitro. While D-DT alone did not have a significant effect on in vitro fibroblast wound healing, simultaneous addition of neutralizing MIF antibody resulted in a significant improvement of fibroblast wound healing. Interestingly, expression of the MIF and D-DT receptor CD74 was down-regulated while the MIF receptors CXCR2 and CXCR4 were up-regulated primarily on macrophages indicating that the MIF-CXCR2/4 axis may promote recruitment of inflammatory cells into adipose tissue. Our results describe a reciprocal role of D-DT to MIF in inflamed adipose tissue, and indicate that D-DT may be beneficial in wound repair by improving fibroblast survival and proliferation.

• Authors: Bong-Sung Kim, Pathricia V Tilstam, Soo Seok Hwang, David Simons, Wibke Schulte, Lin Leng, Maor Sauler, Bergita Ganse, Luisa Averdunk, Rüdger Kopp, Christian Stoppe, Jürgen Bernhagen, Norbert Pallua, Richard Bucala
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 21 Issue 1 Pg. 35-45 (01 2017) ISSN: 1582-4934 [Electronic] England
• PMID: 27605340 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Antigens, Differentiation, B-Lymphocyte
• CXCR4 protein, human
• Histocompatibility Antigens Class II
• Receptors, CXCR4
• Receptors, Interleukin-8B
• invariant chain
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Adipose Tissue (metabolism, pathology)
• Animals
• Antigens, Differentiation, B-Lymphocyte (metabolism)
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Down-Regulation (physiology)
• Fibroblasts (metabolism, pathology)
• Histocompatibility Antigens Class II (metabolism)
• Humans
• Inflammation (metabolism, pathology)
• Intramolecular Oxidoreductases (metabolism)
• Macrophages (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (metabolism, pathology)
• Receptors, CXCR4 (metabolism)
• Receptors, Interleukin-8B (metabolism)
• Up-Regulation (physiology)
• Wound Healing (physiology)